The lack of vaccine adjuvants that are both safe and effective is an important public health problem and is a key research priority for the NIH/NIAID. No adjuvants have yet been approved for use with intradermal vaccines. The goal of this phase II STTR project is to move a new adjuvant for intradermal vaccination-small near-infrared lasers that emit brief, non-damaging, non-painful light doses to a small area of skin-to the point of advanced preclinical development. In the phase I project, our team successfully showed that small diode laser systems could augment immune responses to a vaccine in an established mouse model. The phase II project has three specific aims: 1) Design and construct a small near-infrared diode laser device appropriate for clinical use with intradermal vaccines. 2) Show in an animal model that such a device can enhance an intradermal chikungunya virus vaccine, enabling a significant decrease in antigen dose, dose number or both. 3) Show that that laser exposures are tolerable and non-damaging in humans while stimulating skin immune signaling and immune cell mobilization. Laser-based adjuvanting approaches have not been moved beyond academic studies; this phase II project will help move a laser-based adjuvant toward the clinic, at which point it could be licensed as an adjuvant for multiple vaccines. The broad and long-term objectives of this project are to improve vaccines by increasing the range of new adjuvants available for use with vaccine antigens and to expand the application of intradermal vaccines that can offer protection from diseases through safer less painful and more efficient vaccination approaches. Laser design will start with assessment of how the adjuvant would be used in clinical vaccination and will move to iterative prototype development that incorporates these design considerations and leverages our existing laser manufacturing resources. The final prototype will be bench tested to validate consistent achievement of design requirements and a scalable, quality-based manufacturing process will be established. In parallel, three different near infrared lasers will be tested in a mouse vaccine model to determine the specific configuration that best enhances an intradermal vaccine against chikungunya virus. These studies will be conducted by Dr. Satoshi Kashiwagi at the Vaccine and Immunotherapy Center, Massachusetts General Hospital and Dr. Ted Ross at the College of Veterinary Medicine, University of Georgia. They will demonstrate the ability of the laser adjuvant to provide equivalent protection to a non-adjuvanted vaccine at reduced dose size or number. Finally the laser that works best in these mouse studies will be tested in humans to show that it does not hurt or cause any skin damage and produces similar immune stimulating effects in the skin that are seen in mice. This laser will be tested in human subjects of all skin tones to show that skin responses to the laser are not affected by pigmentation. This clinical study will be conducted by Northeast Dermatology Associates, PA. Together these three aims will prepare the laser adjuvant for continued development in preparation for clinical trials.